An essential goal of our work is the isolation of DNA repair deficient fly strains. Significant progress is being made towards obtaining flies lacking Rrp1 protein, a Drosophila repair enzyme with a putative major role in repair of alkylation and oxidative DNA damage. The Rrp1 gene was located in the cytogenetic interval 23C3-23E3 by deficiency mapping. Mutagenesis screens using these deficiencies have been designed to select Rrp1 mutants using two possible phenotypes: female sterility or mutagen sensitivity during pupal stage. Several additional small deficiencies that are close to the Rrp1 gene were recently selected using a large overlapping deficiency. A synthetic Rrp1 mutant that expresses antisense Rrp1 mRNA was constructed by P-element mediated fly transformation and is currently being characterized. Overexpression fly strains expressing wild-type Rrp1 under the control of a heat-inducible promoter were used to characterize the role of Rrp1 in the repair of mutagen-induced DNA damage in somatic tissue. Female flies induced approximately 15-fold for Rrp1 protein prior to mutagen treatment during larval development show an approximately 2-fold reduction in somatic mutation induced by gamma-irradiation, bleomycin or paraquat, but no change in MMS-induced mutation levels. This system will help define the role of Rrp1 in repair of DNA damage in vivo.